This proposal will apply some of the concepts of developmental biology to a study of the possible role of epithelial-stromal interactions in infiltrating ductal carcinoma of the human breast. The general approach will be to view breast carcinoma not as an isolated abnormal entity but as a series of interactions between differing tissue types beginning with alterations of cell growth patterns and progressing through invasion and metastasis. A model in vitro system for co-culturing the breast carcinoma cells with various types of "primitive" stromas for periods of up to 10 days will be developed. The plan is to simulate laboratory conditions which will induce the carcinoma cells to display their capacities for growth, invasiveness and differentiation in a controlled environment. These properties of the cell will be examined in detail by autoradiographic and electron microscopic methods. This type of information could enhance our knowledge of the biological properties of the cancer cells in relationship to surrounding tissues. In the long run biochemical methods could be used to define more precisely the factors which may be of importance in influencing the behavior of cancer cells under various environmental conditions.